Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Cabozantinib showed a significant improvement in progression-free survival (PFS) compared to placebo, with a hazard ratio of 0.22 (p<0.0001). However, there was no statistically significant difference in overall survival (OS), which raises concerns about the clinical effectiveness of the treatment. The uncertainty surrounding the OS data, due to limited follow-up and high levels of censoring, prevents a higher rating.
Cost effectiveness
The cost-effectiveness estimates for cabozantinib are towards the higher end of what NICE considers acceptable, with a probabilistic ICER of £29,016 per QALY gained. The committee noted that the maximum acceptable ICER would be within the lower half of the £20,000 to £30,000 range, indicating that while it may be cost-effective, it is not strongly so.
Quality of life
The evidence regarding HRQoL is limited, with utility values derived from the COSMIC-311 trial being adjusted to align with general population values. The committee preferred using COSMIC-311 utility values for the progression-free state but expressed concerns about the robustness of the post-progression utility values. Overall, the evidence suggests no significant improvement in HRQoL compared to standard care.
Supporting Domains
Safety and Adverse Effects
Cabozantinib has an acceptable safety profile, with adverse events primarily being mild to moderate. The committee noted that while there are risks associated with the treatment, they are manageable and comparable to existing therapies, supporting a positive safety assessment.
Comparator Selection
The only comparator used was best supportive care, which is appropriate given the lack of other NICE-recommended treatments for this specific patient population. However, the absence of other active comparators limits the robustness of the evidence.
Patient Population and Subgroups
The trial population is representative of the intended patient population, with a focus on adults with advanced differentiated thyroid cancer. The committee acknowledged the small size of the population but recognized that it reflects the clinical reality of this rare condition.
Care Pathway Integration
Cabozantinib can be integrated into existing care pathways with some adjustments, particularly in monitoring and follow-up. However, the need for additional considerations in patient management may pose challenges.
Resource Use and Cost Implications
The resource implications of cabozantinib are significant, with concerns raised about the overall budget impact on the Healthcare. The committee noted that while the treatment may provide benefits, the associated costs could be burdensome.
Evidence Quality and Robustness
The evidence base is primarily derived from the COSMIC-311 trial, which, while a Phase 3 study, has limitations including high levels of censoring and uncertainty in OS data. The committee expressed concerns about the robustness of the evidence, particularly regarding long-term outcomes.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty surrounding the cost-effectiveness estimates and the long-term benefits of cabozantinib. The committee acknowledged the unmet need in this patient population but highlighted the need for more data to reduce uncertainty.
